Liraglutide repairs the infarcted heart: The role of the SIRT1/Parkin/mitophagy pathway.
Liraglutide repairs the infarcted heart: The role of the SIRT1/Parkin/mitophagy pathway.
复制标题
DOI：
10.3892/mmr.2018.8371
复制
发表时间：
2018-03
影响因子：
3.4
通讯作者：
Lv R
中科院分区：
文献类型：
--
作者：
Qiao H;Ren H;Du H;Zhang M;Xiong X;Lv R
利拉鲁肽是一种胰升糖素样肽-1受体激动剂，用于治疗2型糖尿病。本研究旨在探讨利拉鲁肽对心肌梗死后心肌梗死的修复作用及其机制。本研究的结果表明，扩大利拉鲁肽的剂量~28天能够减少心肌梗死后的心肌纤维化、炎症反应和心肌死亡。在体外，利拉鲁肽保护心肌细胞线粒体免受慢性缺氧性损伤，抑制线粒体的凋亡途径。在机制上，利拉鲁肽上调NAD依赖的蛋白去乙酰化酶sirtuin-1(SIRT1)的表达，从而增加Parkin的表达，导致有丝分裂激活。保护性的线粒体吞噬逆转了细胞内5‘-三磷酸腺苷的产生，减少了细胞的氧化应激，平衡了氧化还原反应，维持了线粒体的动态平衡。值得注意的是，在阻断胰升糖素样肽1受体或抑制Parkin之后，利拉鲁肽对线粒体的有利作用消失了。综上所述，本研究结果表明利拉鲁肽通过调节SIRT1/Parkin/丝裂原吞噬通路在心肌梗死修复中的保护作用。
Liraglutide is glucagon-like peptide-1 receptor agonist used for treating patients with type 2 diabetes mellitus. The present study aimed to investigate the role and mechanism of liraglutide in repairing the infarcted heart following myocardial infarction. The results of the present study demonstrated that amplification of the dose of liraglutide for ~28 days was able to reduce cardiac fibrosis, inflammatory responses and myocardial death in the post-infarcted heart. In vitro, liraglutide protected cardiomyocyte mitochondria against the chronic hypoxic damage, inhibiting the mitochondrial apoptosis pathways. Mechanistically, liraglutide elevated the expression of NAD-dependent protein deacetylase sirtuin-1 (SIRT1), which increased the expression of Parkin, leading to mitophagy activation. Protective mitophagy reversed cellular adenosine 5′-triphosphate production, reduced cellular oxidative stress and balanced the redox response, sustaining mitochondrial homeostasis. Notably, following blockade of glucagon-like peptide 1 receptor or knockdown of Parkin, the beneficial effects of liraglutide on mitochondria disappeared. In conclusion, the results of the present study illustrated the protective role of liraglutide in repairing the infarcted heart via regulation of the SIRT1/Parkin/mitophagy pathway.
登录
查看更多内容
影响因子：
11.4
作者：
de Souza, Priscila;Guarido, Karla Lorena;Scheschowitsch, Karin;da Silva, Luisa Mota;Werner, Maria Fernanda;Assreuy, Jamil;da Silva-Santos, Jose Eduardo
通讯作者：
da Silva-Santos, Jose Eduardo
影响因子：
7.5
作者：
Chen, Wei Ren;Chen, Yun Dai;Gu, Xiao Fang
通讯作者：
Gu, Xiao Fang
影响因子：
7.4
作者：
D'Onofrio, Nunzia;Servillo, Luigi;Balestrieri, Maria Luisa
通讯作者：
Balestrieri, Maria Luisa
影响因子：
10.3
作者：
Ho, Hsin-Yu;Lin, Chiao-Wen;Yang, Shun-Fa
通讯作者：
Yang, Shun-Fa
利拉鲁肽可能通过调节细胞内钙稳态来直接保护心肌细胞免受再灌注损伤。
DOI：
10.11909/j.issn.1671-5411.2017.01.008
发表时间：
2017-01
期刊：
Journal of geriatric cardiology : JGC
影响因子：
--
作者：
Hu SY;Zhang Y;Zhu PJ;Zhou H;Chen YD
通讯作者：
Chen YD